title: Intermittent hypobaric hypoxia promotes atherosclerotic plaque instability in ApoE-deficient mice.
abstract: OBJECTIVE
  Sudden cardiac death is one of the most frequent causes of death at high altitude. It has been reported that the intermittent normobaric hypoxia experienced by patients with obstructive sleep apnea may enhance the development of atherosclerosis. However, the effect of hypobaric hypoxia, which mimics the ambient air at high altitude, in the development of atherosclerosis has not been investigated.
  
  
  METHODS
  Twenty male ApoE-deficient mice, 8 weeks of age, were subjected to either control conditions or intermittent hypobaric hypoxia (IHH) for 8 weeks. Mice in the IHH group were exposed to a hypobaric chamber that replicated the hypobaric hypoxia conditions found at 4000 m altitude for 8 hours a day.
  
  
  RESULTS
  IHH-exposed mice did not significantly differ from control mice in plasma lipid levels, including triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein. The hematoxylin and eosin-stained sections of the aortic root showed similar plaque size between the groups. However, IHH-treated mice exhibited significantly decreased plaque collagen content, a feature of atherosclerotic plaque stability. Additionally, matrix metalloproteinase (MMP)-9 protein expression was significantly increased, whereas tissue inhibitor of MMP (TIMP)-2 expression was decreased after exposure to IHH.
  
  
  CONCLUSIONS
  IHH may promote atherosclerotic plaque instability in ApoE-deficient mice by changing the balance of MMPs and TIMPs.
authors.affiliation: Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, People's Republic of China.
authors.forename: Sihua
authors.initials: S
authors.lastname: Jiang
authors.forename: Feipeng
authors.initials: F
authors.lastname: Jin
authors.forename: De
authors.initials: D
authors.lastname: Li
authors.forename: Xingmei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Yang
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000399:Air Pressure; D000531:Altitude; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D015415:Biomarkers / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D000860:Hypoxia / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D008055:Lipids; D003094:Collagen